Gene Therapy - a HIV Cure?
posted: 16/02/2009
A bone marrow transplant seems to have rid one man of HIV – and the doctors claim this is the closest thing yet to a cure for HIV. The New England Journal of Medicine has just published the details.
This could lead to new efforts to develop gene therapy for HIV, and this might end the need to take anti-HIV drugs for life. A single bone marrow transplant might be enough to eliminate the virus completely and permanently.
Not for most
But this method is not going to be available generally anytime soon, even to people in developed countries like the UK which have the money and advanced healthcare systems. Personalised bone marrow transplants will not provide a cure for the vast numbers of people living with HIV across the world.
A 42-year-old USA man living in Germany was infected with HIV for 10 years. He was treated with antiretroviral drugs in Berlin for four years, but he then developed leukaemia. Leukaemia is a type of cancer that affects the white blood cells.
Bone marrow transplant two years ago
He was given a bone marrow transplant two years ago (a standard treatment for serious cases of leukaemia), and since then he has not taken any more anti-HIV drugs; and both his HIV and leukaemia seem to have disappeared. He is believed to be the person who has lived longest since stopping his HIV treatment, without showing any further signs of HIV infection.
Full details are published for the first time today in The New England Journal of Medicine. An editorial says it "places further emphasis on gene therapies" for HIV, adding: "The case paves the way for innovative approaches that provide long-lasting viral control with limited toxicities for persons with HIV infection."
First find your bone marrow donor with a HIV genetic resistance gene
The man's treatment began with a search by doctors at Berlin's Charité Hospital for a bone marrow donor with a genetic resistance to HIV. Some people who have been exposed to the virus on many occasions remain uninfected – there is a well known report that some women sex-workers in Nairobi remained uninfected despite exposure to the virus by many sexual partners.
Some people carry a rare mutation of a gene (CCR5) that helps protect those with the gene from HIV. In Western populations between 1 in 100 and 3 in 100 have this protective gene mutation.
The doctors tested 61 potential donors before they found one with the CCR5 genetic mutation, who agreed to the operation. Finding bone marrow donors is always difficult. Giving bone marrow is uncomfortable and has some risks.
Scale of the problem
Gene therapy as a possible HIV treatment or potential cure is not going to come soon for most people. With over 5000 people diagnosed in NorthWest England, simply finding enough donors may not be realistic. In Berlin it took tests on 61 people to find one person who had the right gene and who also agreed to the procedure. It is possible that in time scientists will work out how to grow a few donors' bone marrow cells in the laboratory to treat many people. But for now it seems we would need to repeat the Berlin search for donors to individually match everyone diagnosed. Just for the NW of England, we might need to find over 300,000 potential bone marrow donors - equivalent to everyone living in any of the cities and boroughs of Greater Manchester and Merseyside.
The American recipient of the transplant, who runs a holiday rentals business in the German capital, has undergone regular checks in the two years since the treatment. The doctors have tested his bone marrow, blood and tissues and found no sign of HIV. "For as long as the viral load remains undetectable, this patient will not require antiretroviral therapy," they say in the journal.
Two for one treatment
Speaking last week, Dr Hutter said there had been several previous reports of patients being virus-free following treatment but none to compare with the latest case. "The difference is that in our patient we had a plan. It was not an accident," he added. "It is the longest time someone who has had antiretroviral therapy and stopped has lasted without the virus rebounding. Normally it rebounds within weeks. It is the closest we have come to a cure."
He doesn't explain his treatment plan, but it seems to have been to pick as a donor someone who had matching bone marrow to the Berlin man's, to restore his body's ability to make cancer-free white blood cells, who also had the rare gene that seems to protect people from HIV transmission - a two for one treatment plan.
Bone marrow transplants too risky for most
Dr Hutter said a bone marrow transplant would be too risky as a routine treatment for HIV and too difficult to find donors with the right genetic make-up. But a modification of the approach using gene therapy to give a person HIV-resistance could work, he said.
Even costly treatment that worked permanently to remove HIV would be worthwhile. The Independent, in its report, claimed the price of treatment with antiretrovirals in Europe is €70,000 to €80,000 Euros (£63,000 to £72,000) a year compared with a one-off cost of €20,000 to €30,000 Euros for a bone marrow transplant. However these drug costings seem grossly inflated, AIDS Treatment Update (May 2006) quoted typical UK costs as just £16,000 a year. A single bone marrow transplant would therefore cost slightly more than about one years' HIV drugs. If it worked consistently and was practical, investing in this would pay the NHS from the second year. Over a lifetime that would save much money as well as potentially restoring people to health, free of HIV. But there is no prospect of this in the foreseeable future. Bone marrow transplants are just too risky and complex - attempting to cure HIV by bone marrow transplants could kill or cause serious harm. The risks were only worth it in the Berlin man's case because he would have died soon otherwise from leukaemia.
Dr Hutter said: "When I started in medicine, HIV was completely untreatable. Now the situation has changed completely. Perhaps our case is a glimpse of hope for the future."
Cure, or is HIV still in hiding?
Professor Jay Levy, an Aids specialist at the University of California, and author of the US journal's editorial, said claims that the patient had been cured of HIV would be premature because of the virus's capacity to hide in other parts of the body including the brain, gut, liver and lymphatic system, from which it could always re-emerge.
"Nevertheless, the results... provide further encouragement for those examining approaches to treatment that reduce CCR5 expression in persons with HIV infection," he writes. In 2007, an estimated two million people died from Aids and 2.7 million were newly infected with HIV.
25 years of research: The HIV virus
When the discovery of HIV was announced in 1984, US politicians predicted that a cure for Aids would be found within five years, but it is still a distant prospect. Over the past 10 years, cocktails of effective antiretroviral drugs have been developed to help keep HIV at bay. Eliminating it has proved far more difficult because of the virus's unique nature. HIV integrates itself into an infected person's DNA and attacks the cells the immune system sends to attack it. Once infected, these T-cells take the virus deeper into the body.
Gene therapy is a new approach that harnesses the natural resistance to HIV shared by 3 per cent of people. Experts hope that by tweaking a person's DNA, they can achieve "long-lasting viral control".
Gene genie
Stem cells and gene therapy are likely to be a major source of treatments for many conditions over the coming years. It is very much in its infancy but scientists, doctors and the people who may benefit, are excited about some of the potential treatments now being tested and planned. And Bush's ban on stem cell research has already been lifted by President Obama, who has also announced major funding for stem cell research.
For now we wait to see what progress is made in developing treatments based on the CCR5 gene that provides protection. Any drugs that emerge may be no better than the others we already have. But they would be a new class of drugs and there is hope that such drugs might be far more effective.
source
stem cell technology prospects
New England Journal of Medicine article
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